We propose a series of studies to examine the biochemical correlates of behavioral abnormalities observed in rats in which an analogue of phenylketonuria has been induced through dosages of L-phenylalanine and p-chlorophenylalanine. The model of induced PKU developed in this laboratory exhibits the biochemical symptoms of PKU including the phenylalanine:tyrosine imbalance and a learning impairment that is present after recovery from the immediate effects of treatment which exceeds that produced by general malnutrition. We plan to broaden the psychological test data. Biochemical studies on the blood, brains, and livers of experimental animals treated both pre- and post-natally will be conducted to obtain data relevant to hypotheses for pathogenesis of the mental defect in phenylketonuria. Using this animal model, new approaches to treatment will be explored which may be applicable to human phenylketonuria. The data will be analyzed to investigate the biochemical correlates of behavioral abnormalities and to compare the biochemistry of induced PKU with the human condition. A more complete understanding of the mechanism of PKU as a basis for treatment and the identification of basic associations between biochemistry, brain structure, and behavior are the objectives of the proposed research program.